Lupus erythematosus is an autoimmune disorder which may, but does not always, affect many different organ systems in an affected individual. Lupus erythematosus (hereinafter “lupus”) may affect the heart, lungs, skin, joints, kidneys, nervous system, lymph gland system, blood cells and/or blood vessels. Certain forms of lupus affect only or predominantly the skin. These forms of lupus are the most visible manifestations of the disease.
The immune system of the body is a complex and elaborate mechanism of protection from foreign substances. The immune system provides resistance to foreign cells and substances (e.g., bacteria or virus) that may cause injury, as well as searching out abnormal cells (e.g., cancerous cells) within the body for destruction. The invading or abnormal cells are neutralized by the immune system humoral and cellular components, including lymphocytes, antibodies, mediating (regulating such as lymphokines) systems, and effector (cytotoxic) cells. As an example. the immune system can recognize the invading or abnormal cells (antigens) within the body and produce antibodies (proteins) which attach to the recognized antigens, leading to their removal. Autoimmunity occurs when the immune system produces antibodies to normal cells in the body. This produces inflammation of normal tissue, resulting in damage and loss of function. In other instances, antibodies attach to antigens within the blood plasma to form immune complexes that may be deposited in normal tissue resulting in inflammation and damage.
Women are more susceptible to lupus than men. Over 90% of lupus patients are females aged 13-40 years. Laboratory tests for the presence of lupus include the LE Cell Test, the Anti-Nuclear Antibody Test, and the test for Anti-DNA-Antibodies. Lupus is, however, often recognized by particular clinical manifestations including: (i) arthritis (occurring in 90-95% of persons with systemic lupus), (ii) skin changes, such as a photosensitive induced “butterfly” rash across the bridge of the nose, across the cheeks and/or beneath the eyes, and/or red, raised and scaly patches, known as discoid lupus, anywhere on the body (occurring in 75-80% of persons with lupus), (iii) hematologic abnormalities, such as anemia, leukopenia, and thrombocytopenia (occurring in about 50% of persons with lupus), (iv) kidney impairment (occurring in about 50% of persons with lupus), (v) heart or lung disease, such as an irritation of the heart or lung lining causing pericarditis or pleurisy (occurring in about 30% of persons with lupus), and (vi) neuropsychiatric changes (occurring in about 10% to 20% of persons with lupus).
Etiology
Lupus erythematosus can be divided into subsets which may or may not have overlapping characteristics: discoid lupus, subacute cutaneous lupus, drug-induced lupus and systemic lupus. Patients in whom the disease seems to be confined to the skin are differentiated from those with systemic or “disseminated” involvement.
Discoid lupus, also called chronic discoid lupus or chronic cutaneous lupus produces lesions over the face, but sometimes spread more extensively across the body. The lesions are usually well circumscribed, disk-like plaques of scaling erythema, tending to clear centrally with scarring, depigmentation and atrophy. Photosensitivity is a common feature but may be absent. Roughly 80% to 90% of patients with discoid lupus lesions will not develop any signs and symptoms of systemic lupus.
Subacute cutaneous lupus produces wide spread skin lesions over the trunk and extremities of the patient. The lesions are apt to be less discrete than those of discoid lupus, more widespread, with temporary depigmentation and telangiectasia without scaring or atrophy. Loss of hair without scaring is common, and mild systemic disease, especially involving the joints, accompanied by fever and malaise are often present.
Another distinct subset of lupus is that associated with reaction to certain drugs, appropriately known as drug induced lupus. Serious organ involvement is rare and prognosis for this subset of lupus is excellent, provided the disease is recognized and the offending medication discontinued.
Systemic lupus is a chronic autoimmune disease that often has a relapsing course. The primary therapeutic approach for systemic lupus is to achieve and maintain adequate suppression of the disease with minimal drug mediated side effects. Evaluation of specific symptoms and clinical findings establish the type and extent of organ involvement and overall disease activity. There are two basic goals of drug treatment for lupus. The first goal is to reduce inflammation within the affected tissues. The second goal is to identify and suppress the specific abnormalities of the immune system that are considered responsible for tissue inflammation. The overall therapeutic plan generally groups lupus manifestations into four broad categories based on primary treatment modality used for initial treatment.
Fever, joint pain (arthralgias), arthritis, and serositis (pleurisy or pericarditis) can often be managed effectively by the administration of nonsteroidal, anti-inflammatory drugs (NSAIDs), such as aspirin, salisylates, ibuprofin, naproxen, clinoril, oxaprozin and tolmetin. The most common side-effects include gastrointestinal complaints and the potentiation of peptic ulcers. Acetaminophen derivatives can be safely taken with NSAIDs for added pain relief.
Cutaneous features of systemic lupus are usually most effectively managed with antimalarial drugs, such as hydroxychloroquine, chloroquine and quinacrine. Due to the high rate of cutaneous disease relapse and the safety of low-dose therapy, antimalarial drug is usually prescribed on an indefinite basis for patients displaying lupus skin conditions. Retinoids such as istretinoin (Acutane™) and etretinate (Acitretinz™) demonstrate beneficial results when given orally, with reduction of lesions refractory to traditional antimalarial drug therapy.
More serious organ involvement is generally treated by the administration of a corticosteroid, given orally or intravenously. Prednisone is the most commonly used oral corticosteroid. When oral administration of steroids proves ineffective, intravenous methyl prednisolone pulse therapy (high dose) is often used in the treatment of lupus nephritis and other serious non-renal manifestations, such as hemolytic anemia, central nervous system inflammation (cerebritis), life-threatening low-platelet counts, and severe pleuropericarditis. Mild androgenic compounds such as Danazol™ and dehydroepiandrosterone (DHEA) have also been used in controlling immune thrombocytopenia and severe hemolytic anemia.
DHEA has also been reported to be effective for treating various manifestations of systemic lupus, with a focus upon the reported ability of DHEA to affect the hormonal and immune systems.
Immunosuppressive drugs are a fourth group used in treatment of systemic lupus. These drugs are employed when corticosteroid therapy is ineffective or intolerable for the patient. Immunosuppressive drugs include azathirprine (Imuran™), cyclosporin A (Sandimmune™), alkylating agents (nitrogen mustards, cyclophosphamide, and chlorambucil), and methotrexate. These drugs are sometimes used in combination with corticosteroids.
The above described treatment regimens for lupus often meet with limited success. Hence, the search continues for alternative treatments for lupus.